Causes of DNA mismatch repair deficiency in sebaceous skin lesions demonstrating loss of MLH1 protein expression: constitutional over somatic MLH1 promoter methylation.

ABSTRACT: Approximately 30% of sebaceous skin lesions (or sebaceous neoplasia) demonstrate DNA mismatch repair (MMR)-deficiency. MMR-deficiency can be caused by Lynch syndrome, resulting from germline pathogenic variants in the DNA MMR genes MLH1, MSH2, MSH6 and PMS2, but other causes include somatic MLH1 gene promoter hypermethylation, constitutional MLH1 gene promoter hypermethylation (MLH1 epimutation), or biallelic somatic MMR gene mutations. In colorectal (CRCs) and endometrial cancers (ECs), tumour MMR-deficiency showing loss of MLH1 and PMS2 protein expression (MLH1/PMS2-deficiency) is predominantly caused by somatic MLH1 hypermethylation, however, it is not clear if somatic MLH1 hypermethylation is a cause of MLH1/PMS2-deficiency in sebaceous neoplasia. This study investigated the causes of

SUBMITTER: Joo JE 

PROVIDER: S-EPMC11985684 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature